The primary function of the major AD risk gene Apolipoprotein E (APOE) is in cholesterol transport (Huang and Mahley, 2014), and ApoE-containing lipoproteins bind to all core members of the LDLR receptor family, to LRP5 and likely to LRP6 as well (Figure 2, panel 4; Kim et al., 1998; Magoori et al., 2003; Beffert et al., 2004; Andersen and Willnow, 2006; Jaeger and Pietrzik, 2008; Guttman et al., 2010). This evidence concerns the gene APOE and Alzheimer disease.